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Updated: Apr 28, 2026
Tracing Gene Expression Through Detection of β-galactosidase Activity in Whole Mouse Embryos
Published on: June 26, 2018
Enhanced expression of the β4-galactosyltransferase 2 gene impairs mammalian tumor growth
11] Division of Pathology and Cell Therapy, Chiba Cancer Research Institute, Chiba, Chiba, Japan [2] Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Abstract:
Altered N-glycosylation of membrane proteins is associated with malignant transformation of cells. We found that the expression of the β4-galactosyltransferase 2 (β4GalT2) gene is decreased markedly during the transformation. Here, we examined whether the tumor growth activity of B16-F10 mouse melanoma cells can be reduced by the enhanced expression of the β4GalT2 gene. We isolated a clone, B16-β4GalT2, showing its β4GalT2 transcript 2.5 times higher than a control clone, B16-mock, by transducing its cDNA, and transplanted them subcutaneously into C57BL/6 mice to examine their tumor growth activity. The results showed that the average size of tumors formed with B16-mock cells is 13.1±0.76 mm, whereas that of tumors formed with B16-β4GalT2 cells is 5.1±1.13 mm (P<0.01) 2 weeks after transplantation. Immunohistochemical analyses showed that the apoptosis and the suppression of angiogenesis are induced in the tumors upon transduction of the β4GalT2 gene. To pursue a clinical usefulness of the β4GalT2 gene for suppressing human tumor growth, we injected adenoviruses carrying the human β4GalT2 cDNA into HuH-7 human hepatocellular carcinomas developed in severe combined immunodeficient mice, and observed marked growth retardation of the tumors. The enhancement of the β4GalT2 gene expression in tumors is one of the promising approaches to suppress human tumor growth.
Insights
Enhanced beta-1,4-galactosyltransferase 2 (β4GalT2) gene expression significantly reduced melanoma and hepatocellular carcinoma tumor growth in mice. This suggests β4GalT2 as a promising target for cancer therapy by suppressing tumor growth and angiogenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Glycobiology
Background:
- Altered N-glycosylation of membrane proteins is a hallmark of malignant cell transformation.
- Beta-1,4-galactosyltransferase 2 (β4GalT2) gene expression is significantly decreased during cellular transformation.
Purpose of the Study:
- To investigate the effect of enhanced β4GalT2 gene expression on the tumor growth of B16-F10 mouse melanoma cells.
- To evaluate the potential clinical utility of β4GalT2 gene therapy for suppressing human tumor growth.
Main Methods:
- Generation of a B16-F10 melanoma cell clone (B16-β4GalT2) with 2.5-fold higher β4GalT2 transcript levels compared to control (B16-mock).
- Subcutaneous transplantation of B16-mock and B16-β4GalT2 cells into C57BL/6 mice to assess tumor growth.
- Intratumoral injection of adenoviruses carrying human β4GalT2 cDNA into HuH-7 human hepatocellular carcinomas in immunodeficient mice.
Main Results:
- Tumors formed by B16-β4GalT2 cells were significantly smaller (5.1±1.13 mm) than those formed by B16-mock cells (13.1±0.76 mm) two weeks post-transplantation (P<0.01).
- Immunohistochemical analysis revealed induced apoptosis and suppressed angiogenesis in tumors with enhanced β4GalT2 expression.
- Significant growth retardation of HuH-7 human hepatocellular carcinomas was observed following adenoviral delivery of human β4GalT2 cDNA.
Conclusions:
- Enhanced expression of the β4GalT2 gene effectively suppresses tumor growth in mouse melanoma and human hepatocellular carcinoma models.
- The induction of apoptosis and suppression of angiogenesis are key mechanisms underlying β4GalT2's anti-tumor effects.
- Upregulating β4GalT2 gene expression presents a promising therapeutic strategy for suppressing human tumor growth.
